This project has advanced from our Target-based Assays and Screening Strategies for Chemical Probe and Therapeutic Lead Discovery category In continued and expanded collaboration with Prof. H. Suga (U. Tokyo), Prof. C. Hoffman (Boston College) and Scott Lovell (U. Kansas) the ADST laboratory has developed peptide macrocycles targeting this essential metabolic enzyme of the pathogenic nematode using novel cyclic peptide libraries and affinity selection and enrichment approaches. The work describing the initial phase of this project was published in 2017. This project has resulted in the discovery and characterization of Ipglycermides, the first inhibitor class that potently and selectively inhibits iPGM from all nematodes species thus far tested. A model organism C. elegans systems is being developed to test the activity of membrane permeable analogs on the viability of the organism. The binding site interaction revealed from a co-crystal structure have provided general molecular insights for the design of analogs now being evaluated in across a panel of iPGM orthologs with the eventual aim to evaluate in the secondary cell and model organism assays now under development.